P1366: NEW LYMPHOABLATIVE CONDITIONING REGIME FOR MULTIPLE SCLEROSIS – FIRST RESULTS FROM RUSSIAN PILOT STUDY
Authors: A. Rukavitcyn, D. Fedorenko, V. Sarzhevskij, A. Samoylova, N. Mochkin, V. Bogatyrev, E. Smirnova, A. Bannikova, A. Mamedova, V. Melnichenko
Journal: HemaSphere (2022)

Background: Intermediate-intensity chemotherapy (IDCT) followed by autologous transplantation of hematopoietic stem cells (ASCT) is the standard of treatment for the part of patients with hightly aggressive relapse-remitting multiple sclerosis (RRMS). There are several most used conditioning regimens, previous EBMT recommendations recommended the use of ‘intermediate intensity’ regimen namely cyclophosphamide 200 mg/kg with T-cell depleting. However, there are currently no data on the conduct of randomized studies that would compare the effectiveness and toxicity of different regimens. Aims: Comparison toxicity conditioning regimens Cph+R and Flu/Cph+R as a conditioning regimen before auto-HSCT for the treatment of and MS Methods: In active study with retrospective control included 94 patients with MS, median age 43 years; 64 men and 30 women, RRMS – 31 patients, PPMS – 39 patients, SPMS -24 patients. EDSS score was 1.5 – 7.5 (average 4.5). All patients received HDCT and ASCT in NMSC named after N.I. Pirogov (2018 - 2021). Conditioning regimens: Cph200 (cyclophosphamide 200 mg/kg 4 days + Rituximab 500 mg/m2 1 day) – 49 patients, Flu/Cph (Fludarabine 150mg/m2 + 6 days + cyclophosphamide 100 mg/kg 2 days + Rituximab 500 mg/m2 1 day) – 45 patients. Results: Hematologic toxicity of different regimens Cph+R, Flu/Cph+R: Duration of neutropenia was– 7-12 days (average 9.6) in Cph+R group and 3-10 (average 6.3) in Flu/Cph+R group. Duration of thrombocytopenia in Cph+R regimen – 7.7 days, Flu/Cph+R -3.4 days. There are 31 (63%) patients received platelet transfusion in Cph+R group and 6 (12%) patients in Flu/Cph+R group. Anemia Grade II (CTCAE 5.0, 2017) was identified in booth regimens. Anemi grade III was most commonly appear in Flu/Cph+R regime (n=4 – 8%). Range of immunosuppression: The minimal count of lymphocytes was significant lower in Flu/Cph+R group 0,0001 – 0,1 х109/l (average 0.008х109/l), than in Cph+R group witch minimal count of lymphocyte was (0,001 – 0,1 х109/l (average 0.03х109/l) (p<0.05) (pic. 1). Non-hematologic toxicity. Oral mucositis (WHO criteria) was observed at 13 (26%) patients Cph+R group (Grade I - 61,5 %; Grade II - 38,5 %) in Flu/Cph+R 4 (9%) patients (Grade I - 100 %). Enteropathy more common at Cph+R group - 16 % (n=8), Grade I -10%, Grade II – 4%, Grade III – 2%, in Flu/Cph+R – 2 (4%) patients had enteropathy (Grade II). Cardiotoxic effects was observed once at Cph+R group (atrial fibrilation), no cases in Flu/Cph+R group. Hepatic toxicity (CTCAE 5.0, 2017) was observed at 9 (18%) patients Cph+R group (Grade I - 10%; Grade II - 8%) in Flu/Cph+R 9 (20%) patients (Grade I - 15 %, Grade II – 5%). Infection in Cph+R group 13 (26%) patients had infection complications (7 local infections, 6 blood stream infections), in Flu/Cph+R – 5 (10%) patients had infection complications complications -1 local infection, 1 catheter –related infection, 3 neutropenic fever). There are no cases of transplant-related mortality in booth regimes. Summary/Conclusion: The effectiveness of the IDCT method in the treatment of aggressive forms of multiple sclerosis has been proven, at the same time, this method has significant limitations due to high toxicity. Our regime (Flu/Cph+R) showed a significantly deeper lymphodepletion, with less toxicity and a reduced incidence of infectious complications. Thus, this method can be applied to the larger number of patients.